Inhibition of interaction between a virus and its receptor is one approach for anti-viral therapy. This proposal is for support of on-going X-ray crystallographic studies of the structure of human CD4, the receptor for HIV. Two different recombinant fragments, containing residues 1-183 and 1- 375 respectively, have been crystallized. The crystals of the "two domain" fragment CD4 (1-183) permit a structure determination and refinement to 2.5 A resolution. This structure will then be used to aid in determining the structure of the complete extracellular fragment, CD4 (1-375), to at least 4 A resolution. Efforts will also be made to improve the resolution afforded by crystals of CD4 (1-375). Site-directed mutants of Cd4 will be designed to complement existing data, in order to map the precise contact surface for gp 120 and to outline the contact surface for class II MHC antigens. Collaboration with efforts to obtain crystals of gp 120/CD4 complexes is also proposed. The structural results will be useful in the design of anti-HIV agents for treatment of AIDS